Sevoflurane anesthesia alters exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.
BACKGROUND
Preexisting cognitive impairment and advanced age are factors that increase the risk of developing postoperative cognitive dysfunction. Because anesthetic agents interfere with cholinergic transmission and as impairment of cholinergic function is associated with cognitive decline, the authors studied how the volatile anesthetic sevoflurane affects exploratory and anxiety-like behavior in young and aged animals with a genetically modified cholinergic system.


METHODS
Young and aged wild-type and mutant mice lacking the beta2 subunit of the nicotinic cholinergic receptor (beta2KO) were anesthetized for 2 h with 2.6% sevoflurane in oxygen and compared with nonanesthetized controls. Locomotor activity and organization of movement in the open field model were assessed before and 24 h after anesthesia. Locomotor activity and anxiety-like behavior in the elevated plus maze were assessed 24 h after anesthesia. High- and low-affinity nicotinic receptor and cholinergic uptake site densities were evaluated in the hippocampus, amygdala, and forebrain regions using receptor autoradiography.


RESULTS
Sevoflurane anesthesia significantly reduced locomotor activity, altered temporospatial organization of trajectories, and increased anxiety-like behavior in young beta2KO mice, whereas no such changes were observed in young wild-type mice. Aged wild-type and beta2KO mice displayed reactions that were similar, but not identical, to the reactions of young mice to sevoflurane anesthesia. However, behavioral changes were not associated with differences in nicotinic receptor or cholinergic uptake site densities.


CONCLUSIONS
In conclusion, sevoflurane anesthesia altered exploratory and anxiety-like behavior in mice lacking the beta2 nicotinic acetylcholine receptor subunit.
Wiklund
Andreas
A
Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden. andreas.wiklund@karolinska.se
Granon
Sylvie
S
Cloëz-Tayarani
Isabelle
I
Faure
Philippe
P
le Sourd
Anne-Marie
AM
Sundman
Eva
E
Changeux
Jean-Pierre
JP
Eriksson
Lars I
LI
D000367:Age Factors; D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000172:deficiency* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000235:genetics; D000077149:Sevoflurane
D008738:Methyl Ethers; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D000077149:Sevoflurane